2.1. THE ROLE OF RETROVIRUSES IN AUTOIMMUNE DISEASE
Retroviral etiology for several human autoimmune diseases has been proposed, and is the subject of some controversy (Pincus, 982, Arthritus Rheum. 25: 847-856; Norval, 1979, Annals of the Rheumatic Diseases 3:8:507-513; Hart et al., 1979, Annals of the Rheumatic Diseases 38:514-525; Deman et al., 1976, Transplantation Reviews 31:79-115; Talal, 1978, in "Autoimmunity: Genetic, Immunologic, Virologic and Clinical Aspects," Academic Press, London). It has been demonstrated that self-reactive antibodies in autoimmune diseases, called autoantibodies, may react with components of retroviruses. For example, Rucheton et al. (1987, Biology of the Cell 60:71-72) reports that human autoantibodies reactive with HnRNP, a human ribonucleoprotein molecule also react with the p30 gag protein of a mouse retrovirus.
Often experiments linking retroviruses with particular autoimmune diseases have failed to produce consistent results. For example, Phillips et al. (1978, Annals of the Rheumatic Diseases 35:422-428) reported isolating a retrovirus from the placenta of a systemic lupus erythematosus (SLE) patient, after previously being unable to do so (Phillips et al., 1976, Annals of the Rheumatic Diseases 35:422-428). Further, particles resembling retroviruses have been observed in placentas of SLE patients at a higher frequency than normal placentas (Imamura et al., 1976, Am. J. Pathol. 83:3:383-394) but interestingly, have not been observed in organs typically involved by SLE (e.g. spleen and kidney).
The literature indicates that a number of researchers are exploring the role of retroviruses in autoimmune disease. For example, Ono et al. (1985, Keio Journal of Medicine 34:1-16), reasoning that the thymus gland is frequently involved in autoimmune disease, cultured thymus cells of autoimmune patients (mainly afflicted with myasthenia gravis, ulcerative colitis, or pure red cell aplasia) with B cells and observed the appearance of retrovirus particles in the cultured thymus cells. Suni et al. (1981, Int. J. Cancer 28:559-566) observed that an antigen related to a retroviral p30 antigen was expressed in highly differentiated syncytiotrophoblasts in human placenta, and suggested that retrovirus-reactive antibodies may represent an autoimmune-like immune response to p30 related antigen which may have escaped during cellular damage (see also Maeda, 1985, Clin. Exp. Immunol. 60:645-653). Kam-Hansen et al. (1989, Acta Neurol. Scand. 80:467-471) has suggested a role for retroviruses in multiple sclerosis. Leiter et al. (1986, J. Exp. Med. 163:87-100) describes a mouse animal model system for diabetes and suggests that retroviral proteins, normally sequestered within pancreatic beta cells, may be expressed on the cell surface as a result of high serum glucose, resulting in autoimmune elimination of glucose-stressed beta cells.
Interestingly, AIDS has been hypothesized to be, at least in part, an autoimmune disease directed at the immune system and triggered by a lymphotrophic retrovirus (Ziegler and Stites, 1986, Clin. Immunol. Immunopathol. 41:305-313). Ziegler and Stites (ibid) have suggested that HIV antigens expressed on the lymphocyte surface may mimic MHC antigens, provoking an autoimmune attack on MHC-bearing cells. Ascher and Sheppard (1988, Clin. Exp. Immunol. 73:165-167) propose that latency of AIDS is not due to delayed viral expression and growth but rather to the accumulation of insults to an immune system with abnormal regulatory mechanisms induced by HIV infection of macrophages.